This application proposes the fourth renewal of the UNC Breast Cancer SPORE. Originally funded in 1992, the UNC SPORE has used significant institutional investment and the distinctive SPORE elements: funding flexibility, interdisciplinary collaboration, bidirectional translational research, developmental programs, and interSPORE partners to build an outstanding program in translational breast cancer research. The UNC SPORE'S combination of population-based research, molecular genetics, breast cancer biology, health disparities research, tissue-acquiring clinical trials, database development, and expertise in bioinformatics and biostatistics was made possible with long-term SPORE support. Interaction between disciplines has resulted in substantial productivity, as measured by important findings published in high impact journals, career advancement for junior investigators, developmental research leading to grants and new SPORE projects, multiple funded interSPORE collaborations, and innovative approaches to breast cancer etiology, classification, prognosis, and therapy. Our projects are conceptually linked by studies of breast cancer molecular intrinsic subtypes, particularly the triple negative breast cancers, basal-like cancer and a newly-defined subtype, Claudin low. We feature a nation leading population science study of breast cancer and minority disparities, the Carolina Breast Cancer Study (CBCS), entering its 20th year of SPORE funding. Our molecular genetics translational group is developing new technology for intrinsic subtyping with which to analyze clinically-annotated samples from CBCS and local, national, and international trials. Novel translational studies of gene expression, tumor microevironment and a systems approach to the kinome will utilize both preclinical models and human tumors. The projects are entitled: 1) Carolina Breast Cancer Study: Genomic and epidemiologic determinants of breast cancer minority disparities. 2) Targeting the infiltrating immune cells in Claudin-low tumors. 3) Development and validation of predictive markers for triple negative breast cancers. 4) Stromal response subtypes in breast cancer risk and progression 5) Quantitative proteomic analysis of the human kinome in Claudin-low and basal-like breast cancer Five of the co-Project leaders are products of the SPORE career development program. Two of the projects resulted from our SPORE Developmental Research Program. The SPORE is supported by exceptional infrastructure and institutional commitment from the UNC Lineberger Comprehensive Cancer Center and three SPORE-funded cores: Pathology, Genomics, Biostatistics & Bioinformatics, and Administration.